Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Impacts of the COVID-19 pandemic on antimicrobial use in companion animals in an academic veterinary hospital in North Carolina.

Antimicrobial resistance (AMR) in bacterial pathogens reduces the effectiveness of these drugs in both human and veterinary medicine, making judicious antimicrobial use (AMU) an important strategy for its control. The COVID-19 pandemic modified operations in both human and veterinary healthcare delivery, potentially impacting AMU. The goal of this research is to quantify how antimicrobial drug prescribing practices for companion animals in an academic veterinary hospital changed during the pandemic. A retrospective study was performed using prescribing data for dogs and cats collected from the NC State College of Veterinary Medicine (NCSU-CVM) pharmacy, which included prescriptions from both the specialty referral hospital and primary care services. Records (n = 31,769) for 34 antimicrobial drugs from 2019-2020-before and during the pandemic-related measures at the NCSU-CVM-were compared. The prescribed antimicrobials' importance was categorized using the FDA's Guidance for Industry (GFI #152), classifying drugs according to medical importance in humans. A proportional odds model was used to estimate the probability of more important antimicrobials being administered in patients seen during the pandemic versus before (i.e., critically important vs. highly important vs. important). Rates of AMU per week and per patient visit were also compared. During the pandemic, cumulative antimicrobials prescribed per week were significantly decreased in most services for dogs. Weekly rates for Highly Important antimicrobials were also significantly lower in dogs. For important and critically important antimicrobials, rates per week were significantly decreased in various services overall. Rates of antimicrobial administration per patient visit were significantly increased for Highly Important drugs. Patients in the internal medicine, dermatology, and surgery services received significantly more important antimicrobials during the pandemic than before, while cardiology patients received significantly less. These results suggest that the pandemic significantly impacted prescribing practices of antimicrobials for companion animals in this study.

TRPV1 Agonist, Capsaicin, Induces Axon Outgrowth after Injury via Ca2+/PKA Signaling.

Preconditioning nerve injuries activate a pro-regenerative program that enhances axon regeneration for most classes of sensory neurons. However, nociceptive sensory neurons and central nervous system neurons regenerate poorly. In hopes of identifying novel mechanisms that promote regeneration, we screened for drugs that mimicked the preconditioning response and identified a nociceptive ligand that activates a preconditioning-like response to promote axon outgrowth. We show that activating the ion channel TRPV1 with capsaicin induces axon outgrowth of cultured dorsal root ganglion (DRG) sensory neurons, and that this effect is blocked in TRPV1 knockout neurons. Regeneration occurs only in NF200-negative nociceptive neurons, consistent with a cell-autonomous mechanism. Moreover, we identify a signaling pathway in which TRPV1 activation leads to calcium influx and protein kinase A (PKA) activation to induce a preconditioning-like response. Finally, capsaicin administration to the mouse sciatic nerve activates a similar preconditioning-like response and induces enhanced axonal outgrowth, indicating that this pathway can be induced in vivo. These findings highlight the use of local ligands to induce regeneration and suggest that it may be possible to target selective neuronal populations for repair, including cell types that often fail to regenerate.

An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK.

A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons.